title: Cholinergic activity correlates with reserve proxies in Alzheimer's disease.
abstract: The clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain "reserve capacity." A possible association between the cholinergic system and reserve is suggested by preclinical observations that the cholinergic system allows cortical plasticity and by clinical observations of variable responses to cholinergic treatments depending on the patient's educational level. The aim of this study was to investigate the association of reserve proxies, that is, education and occupation, with acetylcholinesterase (AChE) activity, measured voxelwise by [(11)C]-MP4A and positron emission tomography (PET), in 9 healthy controls (HC), 7 patients with early probable AD, and 9 subjects with mild cognitive impairment (MCI) at the time of PET imaging, who progressed to AD at follow-up (prodromal AD). The analysis of prodromal and early AD showed positive correlations between education and AChE activity in the hippocampus, bilaterally, and between occupation and AChE activity in the right posterior cingulate gyrus. The significant correlation between AChE activity in structures belonging to the memory network and reserve proxies suggests that the brain reserve in AD is associated with a preserved/stimulated cholinergic neurotransmission.
authors.affiliation: Geneva University and Geneva University Hospital, Geneva, Switzerland. valentina.garibotto@hcuge.ch
authors.forename: Valentina
authors.initials: V
authors.lastname: Garibotto
authors.forename: Marco
authors.initials: M
authors.lastname: Tettamanti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.forename: Ioana
authors.initials: I
authors.lastname: Florea
authors.forename: Andrea
authors.initials: A
authors.lastname: Panzacchi
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Moresco
authors.forename: Jere R
authors.initials: JR
authors.lastname: Virta
authors.forename: Juha
authors.initials: J
authors.lastname: Rinne
authors.forename: Stefano F
authors.initials: SF
authors.lastname: Cappa
authors.forename: Daniela
authors.initials: D
authors.lastname: Perani
mesh_terms: D000085:Acetates; D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002247:Carbon Isotopes; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D058245:Cognitive Reserve / Q000502:physiology*; D004522:Educational Status; D004651:Employment; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010880:Piperidines; D049268:Positron-Emission Tomography; D011859:Radiography; D018709:Statistics, Nonparametric; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D000085:Acetates; D002247:Carbon Isotopes; C100518:N-methyl-4-piperidyl acetate; D010880:Piperidines; D019788:Fluorodeoxyglucose F18; D000109:Acetylcholine
keywords: Acetylcholinesterase (AChE) activity; Alzheimer's disease (AD); Positron emission tomography (PET); Reserve